We request support for a multidisciplinary program within the Department of Medical Viral Oncology using the integrated contributions of existing groups and new laboratories in order to describe mechanisms of malignant cellular transformation and find means for its control. Our approach to this goal depends heavily upon studying the control of viral expression, because viruses can provide a powerful tool for uncovering fundamental cellular processes. We shall approach this goal by seven routes, corresponding to the following units: the first unit describes means to develop selective viral inhibitors; the second, studies of a potentially oncogenic DNA virus which may accomplish genetic transfer between cells; the third, studies of replication of a second tumorigenic DNA virus and the role of histones in DNA replication; the fourth, studies of physiological and chemical controls of potentially oncogenic RNA viruses; the fifth, genetic and biochemical studies of the balance of viral and cellular expression in persistent and lytic infection; the sixth, studies of some of the events during an immunological response to oncogenic viruses; and the seventh, clinical studies in viral pathogenesis and chemotherapy. Thus, we present projects which would range through the molecular and subcellular levels to the cellular and organismic levels, describe physiological and pharmacological mechanisms for viral inhibition, and yield knowledge of fundamental processes and knowledge which is used in clinical application. Since the proposed program combines the efforts of scientists trained in biochemistry, cell biology, immunology, molecular biology, pharmacology, and virology, both the intellectual perspectives available and the methods used would be correspondingly diverse. We believe that interaction among these disciplines would yield new approaches to problems in expression of genetic information, in mechanisms of malignant transformation, and in therapy of cancer. BIBLIOGRAPHIC REFERENCE: Mayhew, E., Paphadjopoulos, D., O'Malley, J.A., Carter, W.A. and Vail, W.J. Cellular uptake and protection against virus infection by polyinosinic polycytidylic acid entrapped within phospholipid vesicles. Molec. Pharmacol. 13: 1977, in press.